PubMed Health⌕ Search

Biomedical subjects

V L Scofield

Publications and source records attributed to V L Scofield.

10 recordsLinked to original sources
PubMed1998

Sperm as infection-potentiating cofactors in HIV transmission.

In this paper I will discuss the possible role of sperm as cofactors in the genital-mucosal transmission of HIV. The ideas involved arose from my laboratory's discovery that sperm bind to HLA-DR molecules expressed on somatic cells, and from our subsequent findings that lymphocytes are activated by these interactions. Sperm binding to HLA-DR mimics one of the two ligand binding characteristics of superantigens, which also bind to T-cell receptors in a V-beta-specific fashion. This property of sperm may be significant in HIV transmission because: (a) HLA-DR plays a central role in immune recognition and response; and (b) cell interactions involving HLA-DR are involved in HIV infection and disease development. After sexual contact, sperm elicit a transient leukocytic infiltration of the mammalian cervix (Thompson, L.A., Barratt, C.L., Bolton, A.E., Cooke, I.D., 1992. The leukocytic reaction of the human cervix. Am. J. Reprod. Immunol. 28, 85; Pandya, I.J., Cohen, J., 1985. The leukocytic reaction of the human uterine cervix to sperm. Fertil. Steril. 43, 417), and human cervical cells are bound and penetrated by sperm at this time (Sievers-Altermann, R., Engelbrecht, D.V., 1990. Entry of spermatozoa into the cervical mucosa and transmission of the AIDS virus. S. Afr. Med. J. 77, 319). At present, little is known about these in vivo events, but sperm-somatic cell interactions in vitro are also followed by sperm entry into the target cell cytoplasm and target cell activation. When the target cells are leukocytes, sperm interactions increase their susceptibility to HIV infection. If similar interactions occur in the cervicovaginal environment after sexual contact, they are likely to enhance the genital-mucosal transfer of HIV from semen.

Disease Transmission, Infectious↗
PubMed1992

Binding of sperm to somatic cells via HLA-DR. Modulation by sulfated carbohydrates.

We have shown previously that human sperm bind and enter leukocytes expressing surface HLA class II molecules. In the present study, mutant B lymphoblastoid cells and HLA-DR-transfected murine 3T3 fibroblasts are used to confirm that HLA class II molecules are somatic cell receptors for sperm. Further, for isolated HLA-DR expressed on murine cells, we show that sperm receptor activity requires the presence of sulfated carbohydrates. As carriers of multiple HLA-DR binding ligands, sperm may 1) mimic the target cell-activating effects of anti-DR antibody and 2) bind HIV through CD4-like or alternate receptors. By these or other mechanisms, sperm/somatic cell interactions in the female reproductive tract may affect fertility and potentiate the sexual transmission of AIDS.

3T3 Cells↗
PubMed1992

Serum amyloid P component (SAP)-like protein from botryllid ascidians provides a clue to amyloid function.

The HA-1 lectin isolated from Botrylloides leachii has an amino acid composition similar to that of mammalian serum amyloid protein (SAP). SAP is a universal component of mammalian amyloid deposits. Like SAP, HA-1 has a disc ultrastructure, and antibody to HA-1 binds both (a) to amyloidlike fibers deposited between rejected Botrylloides colonies and (b) to cerebral amyloid deposits in Alzheimer's disease brains. Deposition of protochordate amyloid within rejection sites and surrounding fouling organisms implies that these fibers function as barriers to allogeneic and infectious challenge. Similarly, mammalian amyloid may also function to contain inflammatory lesions and to limit the spread of certain infections. Pathological amyloidotic conditions in humans, such as Alzheimer's disease, may result from unregulated expression of this primitive encapsulation response.

Alzheimer Disease↗
PubMed1988

Autoreactive blood cells and programmed cell death in growth and development of protochordates.

The tunicate Botryllus is a marine protochordate whose clonal colonies undergo regulated natural transplantations when they come into contact in nature. The outcome of these transplantations (fusion or rejection) is controlled by genes of a highly polymorphic histocompatibility system that resembles in many respects the mammalian major histocompatibility complex (MHC). While fusion or rejection reactions are often completed within 24 hr after transplantation, resorption of one partner of a pair of fused semiallogeneic colonies may occur days to weeks after initial contact. The latter process is similar to the degeneration of old individuals, or zooids, that precedes maturation of each new generation of asexual buds. Here we describe comparisons of in vitro reactions of a) mixtures of cells from allogeneic animals and b) cells taken from animals at the zooid-resorption ("takeover") stage of colony development. In vitro autoreactivity of cells from resorbing colonies may reflect in vivo responses to senescent cells, which in turn may be related to allorecognition events that govern fusion or rejection between colonies.

Animals↗
PubMed1987

Lymphocyte major histocompatibility complex-encoded class II structures may act as sperm receptors.

Human sperm and blood cells were cocultured in vitro to determine whether specific interactions occur between gametes and blood cells. Evidence for cell type-specific sperm binding and penetration of lymphocytes is presented together with findings that suggest that either or both events involve major histocompatibility complex-encoded class II molecules on lymphocytes and a sperm ligand that is immunoreactive with antibodies to T-cell surface antigen T4. Involvement of HLA-DR is suggested by the pattern of sperm interactions with HLA-DR-positive and -negative cells and by inhibition of sperm binding to HLA-DR-positive cells by a monoclonal antibody that identifies a nonpolymorphic determinant on the HLA-DR molecule. That the complementary sperm ligand may be a T4-like structure is suggested by specific inhibition of sperm-lymphocyte binding with monoclonal antibodies OKT4 and OKT4A. The results are discussed in terms of possible roles for immunoglobulin-related structures in human fertilization and in the sexual transmission of the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Separation and labeling of specific subpopulations of Botryllus blood cells.

Blood cells of the colonial tunicate Botryllus were separated by density gradient centrifugation in Percoll. Unseparated blood cells were used to immunize mice for development of hybridoma cell lines producing anti-Botryllus monoclonal antibodies. These antibodies identify specific subpopulations of blood cells, indicating possible divisions of these cells into defined subgroups sharing particular differentiation antigens. Additional studies utilizing fluorescein- conjugated lectins also revealed differential binding to density- and monoclonal antibody-defined blood cell fractions. These methods allow separation of the different Botryllus blood cell types for functional studies.

Animals↗
PubMed1978

Depression of mitogen response in spleen cells from reticuloendotheliosis virus-infected chickens and their suppressive effect on normal lymphocyte response.

Spleen cells and peripheral blood lymphocytes from chickens infected with reticuloendotheliosis virus (REV) were depressed in their responsiveness to phytohemagglutinin (PHA). When spleen cells from uninfected chickens were co-cultured with spleen cells from chickens infected with REV at 2 weeks of age, the PHA response by the normal cells was completely suppressed. Although spleen cells from chickens infected with REV at 6 or 9 weeks of age were also suppressed in their ability to respond to PHA, they did not suppress the mitogenic response of normal cells in mixed cultures.

Aging↗